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Gene Review

RNR2  -  ribonucleotide-diphosphate reductase...

Saccharomyces cerevisiae S288c

Synonyms: CRT6, J1271, Ribonucleoside-diphosphate reductase small chain 1, Ribonucleotide reductase R2 subunit 1, Ribonucleotide reductase small subunit 1, ...
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Disease relevance of RNR2

  • Simultaneous overexpression of RNR2, RNR3 and RNR4 partially rescued the HU hypersensitivity of a ccr4Delta dun1Delta strain, consistent with the notion that the RNR genes are key targets of Crt1 [1].

High impact information on RNR2

  • Each is sensitive to DNA damage. dun1 mutants are also defective for RNR1 and RNR2 induction but are proficient for induction of other genes, defining the existence of at least two distinct DNA damage induction pathways [2].
  • Here, we report the isolation of the WTM (WD40-containing transcriptional modulator) proteins as regulators of Rnr2/Rnr4 localization [3].
  • Wtm1 binds Rnr2/4 complexes and release them to the cytoplasm in response to DNA damage [3].
  • Overproduction of Wtm2 increased Rnr2/Rnr4 [3].
  • In the presence of DNA damage this association is disrupted and Rnr2/Rnr4 become cytoplasmic, where they join with Rnr1 to form an intact complex [3].

Biological context of RNR2


Anatomical context of RNR2

  • CHO-4E cells have 20-40-fold elevated RNR2 protein, reflecting an increased distribution of RNR2 mRNA to the heavy polysomes [8].

Associations of RNR2 with chemical compounds

  • RAD54 and RNR2 reporter activity in response to the DNA damaging agent, methyl methanesulphonate, was measured in ddc1-Delta, rad9-Delta, ddc1-Delta/rad9-Delta, dun1-Delta, crt1-Delta and mbp1-Delta mutants and was compared with that of the wild type [9].
  • Induction of the RNR2 transcript by at least one of these agents, methyl methanesulfonate, did not require protein synthesis [10].
  • In addition, RNR2 induction was not blocked by the presence of cycloheximide and is therefore likely to be independent of protein synthesis [6].
  • RNR2 encodes a 1.5-kilobase mRNA whose levels increase 18-fold after treatment with the DNA-damaging agent 4-nitroquinoline 1-oxide [7].
  • CHO-4E cells display an altered cell cycle with shortened S phase, similar to cells selected for RNR2 overexpression with hydroxyurea [8].

Physical interactions of RNR2

  • GRF1 bound to the UAS2 element of RNR2, which was found to be directly adjacent to the 42-bp fragment [4].

Regulatory relationships of RNR2

  • Nevertheless, Rnr4 is required to activate Rnr2, and the functional species in vivo is believed to be a heterodimeric complex between the two proteins [11].

Other interactions of RNR2


  1. Ccr4 contributes to tolerance of replication stress through control of CRT1 mRNA poly(A) tail length. Woolstencroft, R.N., Beilharz, T.H., Cook, M.A., Preiss, T., Durocher, D., Tyers, M. J. Cell. Sci. (2006) [Pubmed]
  2. DUN1 encodes a protein kinase that controls the DNA damage response in yeast. Zhou, Z., Elledge, S.J. Cell (1993) [Pubmed]
  3. Control of ribonucleotide reductase localization through an anchoring mechanism involving Wtm1. Lee, Y.D., Elledge, S.J. Genes Dev. (2006) [Pubmed]
  4. Identification of the DNA damage-responsive element of RNR2 and evidence that four distinct cellular factors bind it. Elledge, S.J., Davis, R.W. Mol. Cell. Biol. (1989) [Pubmed]
  5. The DNA damage-inducible gene DIN1 of Saccharomyces cerevisiae encodes a regulatory subunit of ribonucleotide reductase and is identical to RNR3. Yagle, K., McEntee, K. Mol. Cell. Biol. (1990) [Pubmed]
  6. DNA damage induction of ribonucleotide reductase. Elledge, S.J., Davis, R.W. Mol. Cell. Biol. (1989) [Pubmed]
  7. Identification and isolation of the gene encoding the small subunit of ribonucleotide reductase from Saccharomyces cerevisiae: DNA damage-inducible gene required for mitotic viability. Elledge, S.J., Davis, R.W. Mol. Cell. Biol. (1987) [Pubmed]
  8. Translational regulation of ribonucleotide reductase by eukaryotic initiation factor 4E links protein synthesis to the control of DNA replication. Abid, M.R., Li, Y., Anthony, C., De Benedetti, A. J. Biol. Chem. (1999) [Pubmed]
  9. DNA-damage induction of RAD54 can be regulated independently of the RAD9- and DDC1-dependent checkpoints that regulate RNR2. Walsh, L., Schmuckli-Maurer, J., Billinton, N., Barker, M.G., Heyer, W.D., Walmsley, R.M. Curr. Genet. (2002) [Pubmed]
  10. Upstream regulatory sequences of the yeast RNR2 gene include a repression sequence and an activation site that binds the RAP1 protein. Hurd, H.K., Roberts, J.W. Mol. Cell. Biol. (1989) [Pubmed]
  11. Structures of the yeast ribonucleotide reductase Rnr2 and Rnr4 homodimers. Sommerhalter, M., Voegtli, W.C., Perlstein, D.L., Ge, J., Stubbe, J., Rosenzweig, A.C. Biochemistry (2004) [Pubmed]
  12. Rnr4p, a novel ribonucleotide reductase small-subunit protein. Wang, P.J., Chabes, A., Casagrande, R., Tian, X.C., Thelander, L., Huffaker, T.C. Mol. Cell. Biol. (1997) [Pubmed]
  13. Isolation of crt mutants constitutive for transcription of the DNA damage inducible gene RNR3 in Saccharomyces cerevisiae. Zhou, Z., Elledge, S.J. Genetics (1992) [Pubmed]
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